[PMID]: | 29223540 |
[Au] Autor: | Luo C; Chen H; Wang Y; Lin G; Li C; Tan L; Su Z; Lai X; Xie J; Zeng H |
[Ad] Endereço: | Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. |
[Ti] Título: | Protective effect of coptisine free base on indomethacin-induced gastric ulcers in rats: Characterization of potential molecular mechanisms. |
[So] Source: | Life Sci;193:47-56, 2018 Jan 15. |
[Is] ISSN: | 1879-0631 |
[Cp] País de publicação: | Netherlands |
[La] Idioma: | eng |
[Ab] Resumo: | AIMS: The aim of this study was to comparatively investigate the potential gastroprotective effect and underlying mechanisms of coptisine free base (CFB, 8-hydroxy-7, 8-dihydrocoptisine), berberine and lansoprazole against indomethacin-induced gastric ulcer in rats. MATERIALS AND METHODS: CFB (10, 20 and 40mg/kg), berberine (20mg/kg) and lansoprazole (30mg/kg) were orally administrated to rats prior to indometacin ingestion, and gastric lesions were evaluated macroscopically and histologically, and further analyzed by ELISA, qRT-PCR and Western blot. KEY FINDINGS: CFB exerted comparable or superior gastroprotective effect to berberine in protecting against indomethacin-induced gastric injury. CFB pretreatment significantly enhanced the levels of superoxide dismutase (SOD) and glutathione (GSH), and markedly decreased the malonaldehyde (MDA) content. CFB administration effectively suppressed the levels of myeloperoxidase (MPO), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II). Besides, CFB substantially up-regulated the mRNA expressions of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and promoted gastric mucosal prostaglandin E level (PGE ). Furthermore, CFB pretreatment remarkably increased the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) from cytosol into the nucleus, and the expression of heme oxygenase-1 (HO-1), while significantly decreased the expression of mitogen activated protein Kinase Kinase 6 (MKK6) and translocation of p38 mitogen-activated protein kinase (p38 MAPK). SIGNIFICANCE: This was the first investigation reporting the anti-ulcer effect of protoberberine alkaloid free base on in vivo rodent model. The gastroprotective mechanism of CFB might involve favorable regulation of antioxidant and anti-inflammatory status mediated, at least partially, by the Nrf2 signaling pathway and p38 MAPK translocation. |
[Mh] Termos MeSH primário: |
Berberina/análogos & derivados Úlcera Gástrica/tratamento farmacológico
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[Mh] Termos MeSH secundário: |
Animais Anti-Inflamatórios/farmacologia Antioxidantes/farmacologia Berberina/metabolismo Berberina/farmacologia Berberina/uso terapêutico Ciclo-Oxigenase 1/metabolismo Ciclo-Oxigenase 2/metabolismo Modelos Animais de Doenças Mucosa Gástrica/patologia Indometacina Interleucina-1beta/metabolismo Lansoprazol/farmacologia Lansoprazol/uso terapêutico Masculino Ratos Úlcera Gástrica/patologia Superóxido Dismutase/metabolismo Fator de Necrose Tumoral alfa/metabolismo Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Anti-Inflammatory Agents); 0 (Antioxidants); 0 (Interleukin-1beta); 0 (Tumor Necrosis Factor-alpha); 0GCL71VN14 (coptisine); 0I8Y3P32UF (Berberine); 0K5C5T2QPG (Lansoprazole); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.15.1.1 (Superoxide Dismutase); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); XXE1CET956 (Indomethacin) |
[Em] Mês de entrada: | 1801 |
[Cu] Atualização por classe: | 180108 |
[Lr] Data última revisão:
| 180108 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171211 |
[St] Status: | MEDLINE |
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